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PAF receptor structure: A hypothesis
Author(s) -
Godfroid J. J.,
Dive G.,
LamotteBrasseur J.,
Batt J. P.,
Heymans F.
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536523
Subject(s) - steric effects , receptor , platelet activating factor , clinical chemistry , stereochemistry , chemistry , biophysics , biology , endocrinology , biochemistry
Different hypotheses of the structure of platelet‐activating factor (PAF) receptor based on structure‐activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position‐1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position‐2. The unusual structural properties of non‐PAF‐like antagonists required 3‐D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong “Cache‐oreilles” (ear‐muff) effect, i.e. , two strong electronegative wells (isocontour at −10 Kcal/mole) are located at 180° to each other and at a relatively constant distance. Initial consideration of the “Cache‐oreilles” effect implied the structure of a bipolarized cylinder of 10–12 Å diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi‐polarized cylinder.